Excluding systematic biopsy in favor of MRI-targeted biopsy in men with elevated prostate-specific antigen (PSA) levels reduced the probability of detecting clinically insignificant cancers, but at the risk of missing some clinically significant cancers and delaying their diagnosis, the randomized GÖTEBORG-2 trial from Sweden showed.

Among nearly 18,000 participants, 0.6% of men who underwent MRI-targeted biopsy alone were diagnosed with clinically insignificant prostate cancer (Gleason 3+3) compared with 1.2% of those in a reference group who underwent systematic biopsy, as well as targeted biopsy of suspicious lesions shown on MRI (relative risk [RR] 0.46, 95% CI 0.33-0.64, P<0.001), reported Jonas Hugosson, MD, PhD, of Sahlgrenska University Hospital in Gothenburg, Sweden, and colleagues.

“Since the frequent detection of small Gleason 3+3 cancers after PSA screening is regarded as a major contributor to the high incidence of potentially harmful overdiagnosis of prostate cancer, this finding is of importance,” they wrote in the New England Journal of Medicine.

“This strategy also considerably reduced the percentage of biopsies in participants in the experimental group who had elevated PSA levels,” they added, noting that “prostate biopsy is an unpleasant and potentially risky procedure.”

However, clinically significant cancers (Gleason 3+4) were detected in 0.9% of participants in the experimental group compared with 1.1% in the reference group, meaning that 19% fewer clinically significant cancers were detected in the experimental group (RR 0.81, 95% CI 0.60-1.1).

“Delayed diagnosis in these participants is unlikely to be detrimental, but future follow-up is important,” Hugosson and colleagues wrote.

In an accompanying editorial, Roman Gulati, MS, of Fred Hutchinson Cancer Center in Seattle, noted that “whether the trade-offs of omitting systematic biopsy are acceptable needs to be weighed by the clinical community in the context of contemporary standards of care.”

“The history of PSA screening has shown us that difficult trade-offs between too much and too little diagnosis are inevitable,” he continued. “A reckoning is now needed with regard to whether more acceptable trade-offs can be achieved with the use of variables that are available before diagnosis, such as triage testing or MRI-targeted biopsy, or after diagnosis, such as relabeling clinically insignificant prostate cancer or using appropriate conservative management. The GÖTEBORG-2 trial provides another useful data point.”

The population-based study included men ages 50 to 60 who underwent regular PSA screening. Those with a PSA level of 3 ng/mL or higher underwent further evaluation with MRI. The reference group then underwent systematic biopsy regardless of MRI results. Targeted biopsy was added if MRI revealed suspicious lesions, defined as a score of 3 to 5 measured by the Prostate Imaging Reporting and Data System (PI-RADS). The experimental group underwent MRI-targeted biopsy only.

Hugosson and colleagues noted that the clinically significant cancers that were detected only by systematic biopsy were diagnosed in 10 men in the reference group. Nine of these men had negative MRIs and one had false-positive findings on MRI.

Six of the participants diagnosed with prostate cancer were managed primarily with active surveillance, while three were treated with radical prostatectomy and one was treated with radiation therapy.

The most common adverse events in the two groups were mild and included hematuria and hematospermia. Seven participants in the reference group received prescriptions for antibiotics for outpatient treatment of urinary tract infections within 30 days after biopsy compared with three participants in the experimental group.

A total of five participants were hospitalized within 30 days after biopsy — four in the reference group (two for urosepsis, one for pneumonia, and one for acute hypertension) and one in the experimental group (for urosepsis). No deaths were reported.

Hugosson and colleagues acknowledged that the study had several limitations, including the relatively young age of participants and the single-center design, which could limit generalizability.

“Whether newer biopsy techniques, such as transperineal biopsy and image-guided fusion technology, may improve the diagnostic performance of the screening algorithm is unknown,” they wrote, pointing out that these methods should eventually produce an even larger effect size than that seen in this trial.

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